The Relationship Between Expression Of MMP-9,MMP-2,TIMP-2,PTTG1 Protein,Ki67 And Cathepsin K And Invasion Of Pituitary Adenomas:a Immunohistochemical Study

Background and objectivePituitary adenomas (PAs) are one of the highly prevalent intracranial tumors.Despite the benign nature of PAs, they may invade adjacent structures, such as sphenoid sinus, cavernous sinus, suprasellar structures and so on, making difficult the totally resection of tumor and resulting in a higher rate of recurrence and lower rate of remission. The abnormal expression of some proteins may play an important role in invasiveness of PAs. The objects of the present study are to study the expression difference of MMP9, MMP2, TIMP2, PTTG1 and Ki67 between PAs invading into sphenoid sinus and cavernous sinus and to explore the function of Cathepsin K in sphenoid sinus invasion by immunohistochemistry (IHC).Materials and MethodsInvolve 60 patients with PAs invading sphenoid sinus, 60 patients with PAs invading cavernous sinus and 60 patients with non-invasive PAs. Indirect enzyme-labeled antibody method was used for MMP-9, MMP-2, TIMP-2 and Ki67 and avidin-biotin-pcroxidase complex method (ABC method) was used for PTTG1 and Cathepsin K.Results1. Immunoreactivity of MMP-9, MMP-2, TIMP-2 and Cathepsin K was seen mainly in the cytoplasma. Immunoreactivity of Ki67 was seen primarily in the nuclear.Immunoreactivity of PTTG1 was found in both nuclear and cytoplasma. The immunostaining score for MMP9, MMP2 and PTTG1 in invasive PAs was significantly higher than that in non-invasive PAs (P<0.05). In contrast, the immunostaining score for TIMP2 in invasive PAs was significantly lower than that in non-invasive PAs (P<0.05).2. The immunostaining score for MMP-9 and MMP-2 in PAs with cavernous sinus was significantly higher than that in PAs with sphenoid sinus (P<0.05).3. MMP9 expression was positively correlated with MMP2 expression (r=0.827,p<0.001). TIMP-2 expression was negatively associated with MMP9 and MMP2 expression (r=-0.76, p<0,001 and r=-0.716, p<0.001).4. There was a significant relationship between Cathepsin K expression and sphenoid sinus invasion of PAs (P<0.05).Conclusion1. MMP-9 and MMP-2 may be correlated with invasiveness of PAs, especially cavernous sinus invasion. PTTG1 expression may be associated with invasiveness of PAs.2. TIMP2 may play an important role in prevention and inhibition of tumor invasiveness.3. Cathepsin K may have a great importance in sphenoid sinus or clivus invasion of PAs.